A Study of Tarceva (Erlotinib) Following Platinum-Based Chemotherapy in Patients With Advanced, Recurrent, or Metastatic Non-Small Cell Lung Cancer (NSCLC)

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Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without progressive disease (PD) according to Response Evaluation Criteria in Solid Tumors (RECIST) were randomized to receive a placebo, orally (PO) as tablets, daily, from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive erlotinib, 150 mg/day, PO as tablets from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive a placebo, PO as tablets, daily, from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive erlotinib, 150 mg/day, PO as tablets from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Total of all reporting groups

Overall Number of Baseline Participants

451

438

889

Baseline Analysis Population Description

...

Baseline Analysis Population Description

Full analysis set (FAS): all randomized participants presented according to the therapy that they were randomized to receive

Percentage of Participants With PD According to Response Evaluation Criteria in Solid Tumors (RECIST) or Death (Data Cutoff 17 May 2008)

Description

Progression-free survival (PFS) was defined as the time from randomiza...

Description

Progression-free survival (PFS) was defined as the time from randomization to PD or death, whichever occurred first. For target lesions (TLs), PD was defined at least a 20 percent (%) increase in the sum of the largest diameter (SLD), taking as reference the smallest SLD recorded from baseline (BL) more the appearance of one or more new lesions. For non-target lesions (NTLs), PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing NTLs. Participants without PD or death were censored at the date of last tumor assessment where non-progression was documented.

Time Frame

Screening, BL [≤21 days after randomization], every 6 weeks thereafter until Week 48, every 12 weeks thereafter until PD, discontinuation of study treatment, or end of survival follow-up, up to data cutoff of 17 May 2008 (up to 27 months)

Outcome Measure Data Outcome Measure Data

Analysis Population Description

Analysis Population Description

FAS; participants with PD prior to randomization were excluded from analysis.

Arm/Group Title

Placebo

Erlotinib, 150 mg/Day

Arm/Group Description:

Participants completed 4 cycles (3 ...

Participants completed 4 cycles (3 ...

Arm/Group Description:

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive a placebo, PO as tablets, daily, from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive erlotinib, 150 mg/day, PO as tablets from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Overall Number of Participants Analyzed

447

437

Measure Type: Number

Unit of Measure: percentage of participants

89.5

79.9

2.Primary Outcome

Title

PFS in All Participants (Data Cutoff 17 May 2008)

Description

The median time, in weeks, from randomization to PFS event. Participan...

Description

The median time, in weeks, from randomization to PFS event. Participants without PD or death were censored at the date of last tumor assessment where non-progression was documented. The 95% confidence interval (CI) was estimated using Kaplan-Meier methodology.

Time Frame

Screening, BL (≤21 days after randomization), every 6 weeks thereafter until Week 48, every 12 weeks thereafter until PD, discontinuation of study treatment, or end of survival follow-up, up to data cutoff of 17 May 2008 (up to 27 months)

Outcome Measure Data Outcome Measure Data

Analysis Population Description

Analysis Population Description

FAS; participants with PD prior to randomization were excluded from analysis.

Arm/Group Title

Placebo

Erlotinib, 150 mg/Day

Arm/Group Description:

Participants completed 4 cycles (3 ...

Participants completed 4 cycles (3 ...

Arm/Group Description:

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive a placebo, PO as tablets, daily, from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive erlotinib, 150 mg/day, PO as tablets from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

PFS was defined as the time from randomization to PD or death, whichev...

Description

PFS was defined as the time from randomization to PD or death, whichever occurred first. For TLs, PD was defined at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from BL more the appearance of one or more new lesions. For NTLs, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing NTLs. Participants without PD or death were censored at the date of last tumor assessment where non-progression was documented. The 95% CI was estimated using Kaplan-Meier methodology.

Time Frame

6 months

Outcome Measure Data Outcome Measure Data

Analysis Population Description

Analysis Population Description

FAS; participants with PD prior to randomization were excluded from analysis.

Arm/Group Title

Placebo

Erlotinib, 150 mg/Day

Arm/Group Description:

Participants completed 4 cycles (3 ...

Participants completed 4 cycles (3 ...

Arm/Group Description:

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive a placebo, PO as tablets, daily, from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive erlotinib, 150 mg/day, PO as tablets from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

PFS was defined as the time from randomization to PD or death, whichev...

Description

PFS was defined as the time from randomization to PD or death, whichever occurred first. For TLs, PD was defined at least a 20% increase in the SLD, taking as reference the smallest SLD recorded since treatment started or the appearance of one or more new lesions. For NTLs, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing NTLs. Participants without PD or death were censored at the date of last tumor assessment where non-progression was documented.

Time Frame

Screening, BL (≤21 days after randomization), every 6 weeks thereafter until Week 48, every 12 weeks thereafter until PD, discontinuation of study treatment, or end of survival follow-up, up to data cutoff of 17 May 2008 (up to 27 months)

Outcome Measure Data Outcome Measure Data

Analysis Population Description

Analysis Population Description

FAS; only participants with EGFR IHC positive tumors were included in the analysis.

Arm/Group Title

Placebo

Erlotinib, 150 mg/Day

Arm/Group Description:

Participants completed 4 cycles (3 ...

Participants completed 4 cycles (3 ...

Arm/Group Description:

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive a placebo, PO as tablets, daily, from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive erlotinib, 150 mg/day, PO as tablets from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Overall Number of Participants Analyzed

311

307

Measure Type: Number

Unit of Measure: percentage of participants

89.4

79.5

5.Primary Outcome

Title

PFS in EGFR IHC Positive Population (Data Cutoff 17 May 2008)

Description

The median time, in weeks, from randomization to PFS event. Participan...

Description

The median time, in weeks, from randomization to PFS event. Participants without PD or death were censored at the date of last tumor assessment where non-progression was documented. The 95% CI was estimated using Kaplan-Meier methodology.

Time Frame

Screening, BL (≤ 21 days after randomization), every 6 weeks thereafter until Week 48, every 12 weeks thereafter until PD, discontinuation of study treatment, or end of survival follow-up, up to data cutoff of 17 May 2008 (up to 27 months)

Outcome Measure Data Outcome Measure Data

Analysis Population Description

Analysis Population Description

FAS;only participants with EGFR IHC positive tumors were included in the analysis.

Arm/Group Title

Placebo

Erlotinib, 150 mg/Day

Arm/Group Description:

Participants completed 4 cycles (3 ...

Participants completed 4 cycles (3 ...

Arm/Group Description:

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive a placebo, PO as tablets, daily, from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive erlotinib, 150 mg/day, PO as tablets from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Overall Number of Participants Analyzed

311

307

Median (95% Confidence Interval)

Unit of Measure: weeks

11.1

(7.1 to 11.7)

12.3

(12.0 to 17.7)

Statistical Analysis 1
Statistical Analysis 1

Statistical Analysis Overview

Comparison Group Selection

Placebo, Erlotinib, 150 mg/Day

Comments

[Not Specified]

Type of
Statistical Test

Superiority or Other

Comments

[Not Specified]

Statistical Test of Hypothesis

P-Value

< 0.0001

Comments

[Not Specified]

Method

Log Rank

Comments

[Not Specified]

Method of Estimation

Estimation Parameter

Hazard Ratio (HR)

Estimated Value

0.69

Confidence Interval

(2-Sided) 95%

0.58
to 0.82

Estimation Comments

[Not Specified]

6.Primary Outcome

Title

Probable Percentage of Participants in the EGFR IHC Positive Population Remaining Alive and Progression Free at 6 Months (Data Cutoff 17 May 2008)

Description

PFS was defined as the time from randomization to PD or death, whichev...

Description

PFS was defined as the time from randomization to PD or death, whichever occurred first. For TLs, PD was defined at least a 20% increase in the SLD, taking as reference the smallest SLD recorded since treatment started or the appearance of one or more new lesions. For NTLs, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing NTLs. Participants without PD or death were censored at the date of last tumor assessment where non-progression was documented. The 95% CI was estimated using Kaplan-Meier methodology.

Time Frame

6 months

Outcome Measure Data Outcome Measure Data

Analysis Population Description

Analysis Population Description

FAS; only participants with EGFR IHC positive tumors were included in the analysis.

Arm/Group Title

Placebo

Erlotinib, 150 mg/Day

Arm/Group Description:

Participants completed 4 cycles (3 ...

Participants completed 4 cycles (3 ...

Arm/Group Description:

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive a placebo, PO as tablets, daily, from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive erlotinib, 150 mg/day, PO as tablets from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Overall Number of Participants Analyzed

311

307

Measure Type: NumberNumber (95% Confidence Interval)

Unit of Measure: percentage of participants

16.0

(12.0 to 21.0)

27.0

(22.0 to 32.0)

7.Secondary Outcome

Title

Percentage of All Participants Who Died (Data Cutoff 12 January 2012)

Description

[Not Specified]

Description

[Not Specified]

Time Frame

Screening, BL (≤21 days after randomization), every 6 weeks thereafter until Week 48, every 12 weeks thereafter until PD, discontinuation of study treatment, or end of survival follow-up, up to data cutoff of 12 January 2012 (up to 71 months).

Outcome Measure Data Outcome Measure Data

Analysis Population Description

Analysis Population Description

FAS

Arm/Group Title

Placebo

Erlotinib, 150 mg/Day

Arm/Group Description:

Participants completed 4 cycles (3 ...

Participants completed 4 cycles (3 ...

Arm/Group Description:

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive a placebo, PO as tablets, daily, from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive erlotinib, 150 mg/day, PO as tablets from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

OS was defined as the median time, in months, from the date of randomi...

Description

OS was defined as the median time, in months, from the date of randomization to the date of death, due to any cause. Patients who have not died at the time of the final analysis will be censored at the date the patient was last known to be alive. The 95% CI was estimated using Kaplan-Meier methodology.

Time Frame

Screening, BL (≤ 21 days after randomization), every 6 weeks thereafter until Week 48, every 12 weeks thereafter until PD, discontinuation of study treatment, or end of survival follow-up, up to data cutoff of 12 January 2012 (up to 71 months)

Outcome Measure Data Outcome Measure Data

Analysis Population Description

Analysis Population Description

FAS

Arm/Group Title

Placebo

Erlotinib, 150 mg/Day

Arm/Group Description:

Participants completed 4 cycles (3 ...

Participants completed 4 cycles (3 ...

Arm/Group Description:

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive a placebo, PO as tablets, daily, from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive erlotinib, 150 mg/day, PO as tablets from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

OS was defined as the median time, in months, from the date of randomi...

Description

OS was defined as the median time, in months, from the date of randomization to the date of death, due to any cause. Patients who have not died at the time of the final analysis will be censored at the date the patient was last known to be alive. The 95% CI was estimated using Kaplan-Meier methodology.

Time Frame

1 year

Outcome Measure Data Outcome Measure Data

Analysis Population Description

Analysis Population Description

FAS

Arm/Group Title

Placebo

Erlotinib, 150 mg/Day

Arm/Group Description:

Participants completed 4 cycles (3 ...

Participants completed 4 cycles (3 ...

Arm/Group Description:

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive a placebo, PO as tablets, daily, from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive erlotinib, 150 mg/day, PO as tablets from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Overall Number of Participants Analyzed

451

438

Measure Type: NumberNumber (95% Confidence Interval)

Unit of Measure: percentage of participants

45.0

(41.0 to 50.0)

50.0

(45.0 to 55.0)

10.Secondary Outcome

Title

Percentage of EGFR IHC Positive Participants Who Died (Data Cutoff 12 January 2012)

Description

[Not Specified]

Description

[Not Specified]

Time Frame

Screening, BL (≤21 days after randomization), every 6 weeks thereafter until Week 48, every 12 weeks thereafter until PD, discontinuation of study treatment, or end of survival follow-up, up to data cutoff of 12 January 2012 (up to 71 months)

Outcome Measure Data Outcome Measure Data

Analysis Population Description

Analysis Population Description

FAS; only participants with EGFR IHC positive tumors were included in the analysis.

Arm/Group Title

Placebo

Erlotinib, 150 mg/Day

Arm/Group Description:

Participants completed 4 cycles (3 ...

Participants completed 4 cycles (3 ...

Arm/Group Description:

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive a placebo, PO as tablets, daily, from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive erlotinib, 150 mg/day, PO as tablets from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Overall Number of Participants Analyzed

313

308

Measure Type: Number

Unit of Measure: percentage of participants

87.5

80.5

11.Secondary Outcome

Title

OS in EGFR IHC Positive Population (Data Cutoff 12 January 2012)

Description

OS was defined as the median time, in months, from the date of randomi...

Description

OS was defined as the median time, in months, from the date of randomization to the date of death, due to any cause. Patients who have not died at the time of the final analysis will be censored at the date the patient was last known to be alive. The 95% CI was estimated using Kaplan-Meier methodology.

Time Frame

Screening, BL (≤21 days after randomization), every 6 weeks thereafter until Week 48, every 12 weeks thereafter until PD, discontinuation of study treatment, or end of survival follow-up, up to data cutoff of 12 January 2012 (up to 71 months)

Outcome Measure Data Outcome Measure Data

Analysis Population Description

Analysis Population Description

FAS; only participants with EGFR IHC positive tumors were included in the analysis.

Arm/Group Title

Placebo

Erlotinib, 150 mg/Day

Arm/Group Description:

Participants completed 4 cycles (3 ...

Participants completed 4 cycles (3 ...

Arm/Group Description:

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive a placebo, PO as tablets, daily, from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive erlotinib, 150 mg/day, PO as tablets from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Overall Number of Participants Analyzed

313

308

Median (95% Confidence Interval)

Unit of Measure: months

11.0

(9.7 to 12.8)

12.8

(11.1 to 14.7)

Statistical Analysis 1
Statistical Analysis 1

Statistical Analysis Overview

Comparison Group Selection

Placebo, Erlotinib, 150 mg/Day

Comments

[Not Specified]

Type of
Statistical Test

Superiority or Other

Comments

[Not Specified]

Statistical Test of Hypothesis

P-Value

0.0050

Comments

[Not Specified]

Method

Log Rank

Comments

[Not Specified]

Method of Estimation

Estimation Parameter

Hazard Ratio (HR)

Estimated Value

0.78

Confidence Interval

(2-Sided) 95%

0.66
to 0.93

Estimation Comments

[Not Specified]

12.Secondary Outcome

Title

Probable Percentage of Participants in the EGFR IHC Positive Population Remaining Alive at 1 Year (Data Cutoff 12 January 2012)

Description

OS was defined as the median time, in months, from the date of randomi...

Description

OS was defined as the median time, in months, from the date of randomization to the date of death, due to any cause. Patients who have not died at the time of the final analysis will be censored at the date the patient was last known to be alive. The 95% CI was estimated using Kaplan-Meier methodology.

Time Frame

1 year

Outcome Measure Data Outcome Measure Data

Analysis Population Description

Analysis Population Description

FAS

Arm/Group Title

Placebo

Erlotinib, 150 mg/Day

Arm/Group Description:

Participants completed 4 cycles (3 ...

Participants completed 4 cycles (3 ...

Arm/Group Description:

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive a placebo, PO as tablets, daily, from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive erlotinib, 150 mg/day, PO as tablets from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Overall Number of Participants Analyzed

313

308

Measure Type: NumberNumber (95% Confidence Interval)

Unit of Measure: percentage of participants

47.0

(41.0 to 52.0)

52.0

(47.0 to 58.0)

13.Secondary Outcome

Title

Percentage of EGFR IHC Negative Participants With PD or Death (Data Cutoff 17 May 2008)

Description

PFS was defined as the time from randomization to PD or death, whichev...

Description

PFS was defined as the time from randomization to PD or death, whichever occurred first. For TLs, PD was defined at least a 20% increase in the SLD, taking as reference the smallest SLD recorded since treatment started or the appearance of one or more new lesions. For NTLs, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing NTLs. Participants without PD or death were censored at the date of last tumor assessment where non-progression was documented.

Time Frame

Screening, BL (≤21 days after randomization), every 6 weeks thereafter until Week 48, every 12 weeks thereafter until PD, discontinuation of study treatment, or end of survival follow-up, up to data cutoff of 17 May 2008 (up to 71 months)

Outcome Measure Data Outcome Measure Data

Analysis Population Description

Analysis Population Description

FAS; only participants with EGFR IHC negative tumors were included in the analysis.

Arm/Group Title

Placebo

Erlotinib, 150 mg/Day

Arm/Group Description:

Participants completed 4 cycles (3 ...

Participants completed 4 cycles (3 ...

Arm/Group Description:

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive a placebo, PO as tablets, daily, from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive erlotinib, 150 mg/day, PO as tablets from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Overall Number of Participants Analyzed

59

62

Measure Type: Number

Unit of Measure: percentage of participants

89.8

77.4

14.Secondary Outcome

Title

PFS in EGFR IHC Negative Participants (Data Cutoff 17 May 2008)

Description

The median time, in weeks, from randomization to PFS event. Participan...

Description

The median time, in weeks, from randomization to PFS event. Participants without PD or death were censored at the date of last tumor assessment where non-progression was documented. The 95% CI was estimated using Kaplan-Meier methodology.

Time Frame

Screening, BL (≤21 days after randomization), every 6 weeks thereafter until Week 48, every 12 weeks thereafter until PD, discontinuation of study treatment, or end of survival follow-up, up to data cutoff of 17 May 2008 (up to 27 months)

Outcome Measure Data Outcome Measure Data

Analysis Population Description

Analysis Population Description

FAS; only participants with EGFR IHC negative tumors were included in the analysis.

Arm/Group Title

Placebo

Erlotinib, 150 mg/Day

Arm/Group Description:

Participants completed 4 cycles (3 ...

Participants completed 4 cycles (3 ...

Arm/Group Description:

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive a placebo, PO as tablets, daily, from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive erlotinib, 150 mg/day, PO as tablets from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Overall Number of Participants Analyzed

59

62

Median (95% Confidence Interval)

Unit of Measure: weeks

9.0

(6.4 to 12.0)

11.0

(6.6 to 13.1)

Statistical Analysis 1
Statistical Analysis 1

Statistical Analysis Overview

Comparison Group Selection

Placebo, Erlotinib, 150 mg/Day

Comments

[Not Specified]

Type of
Statistical Test

Superiority or Other

Comments

[Not Specified]

Statistical Test of Hypothesis

P-Value

0.1768

Comments

[Not Specified]

Method

Log Rank

Comments

[Not Specified]

Method of Estimation

Estimation Parameter

Hazard Ratio (HR)

Estimated Value

0.77

Confidence Interval

(2-Sided) 95%

0.51
to 1.14

Estimation Comments

[Not Specified]

15.Secondary Outcome

Title

Probable Percentage of Participants in the EGFR IHC Negative Population Remaining Alive and Free of Disease Progression at 6 Months (Data Cutoff 17 May 2008)

Description

PFS was defined as the time from randomization to PD or death, whichev...

Description

PFS was defined as the time from randomization to PD or death, whichever occurred first. For TLs, PD was defined at least a 20% increase in the SLD, taking as reference the smallest SLD recorded since treatment started or the appearance of one or more new lesions. For NTLs, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing NTLs. Participants without PD or death were censored at the date of last tumor assessment where non-progression was documented. The 95% CI was estimated using Kaplan-Meier methodology.

Time Frame

6 months

Outcome Measure Data Outcome Measure Data

Analysis Population Description

Analysis Population Description

FAS; only participants with EGFR IHC negative tumors were included in the analysis.

Arm/Group Title

Placebo

Erlotinib, 150 mg/Day

Arm/Group Description:

Participants completed 4 cycles (3 ...

Participants completed 4 cycles (3 ...

Arm/Group Description:

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive a placebo, PO as tablets, daily, from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive erlotinib, 150 mg/day, PO as tablets from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Overall Number of Participants Analyzed

59

62

Measure Type: NumberNumber (95% Confidence Interval)

Unit of Measure: percentage of participants

11.0

(2.0 to 20.0)

22.0

(11.0 to 34.0)

16.Secondary Outcome

Title

Percentage of EGFR IHC Negative Participants Who Died (Data Cutoff 17 May 2008)

Description

[Not Specified]

Description

[Not Specified]

Time Frame

Screening, BL (≤21 days after randomization), every 6 weeks thereafter until Week 48, every 12 weeks thereafter until PD, discontinuation of study treatment, or end of survival follow-up, up to data cutoff of 17 May 2008 (up to 27 months)

Outcome Measure Data Outcome Measure Data

Analysis Population Description

Analysis Population Description

FAS; only participants with EGFR IHC negative tumors were included in the analysis.

Arm/Group Title

Placebo

Erlotinib, 150 mg/Day

Arm/Group Description:

Participants completed 4 cycles (3 ...

Participants completed 4 cycles (3 ...

Arm/Group Description:

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive a placebo, PO as tablets, daily, from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive erlotinib, 150 mg/day, PO as tablets from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Overall Number of Participants Analyzed

59

62

Measure Type: Number

Unit of Measure: percentage of participants

50.8

41.9

17.Secondary Outcome

Title

OS in EGFR IHC Negative Participants (Data Cutoff 17 May 2008)

Description

OS was defined as the median time, in months, from the date of randomi...

Description

OS was defined as the median time, in months, from the date of randomization to the date of death, due to any cause. Patients who have not died at the time of the final analysis will be censored at the date the patient was last known to be alive. The 95% CI was estimated using Kaplan-Meier methodology.

Time Frame

Screening, BL (≤21 days after randomization), every 6 weeks thereafter until Week 48, every 12 weeks thereafter until PD, discontinuation of study treatment, or end of survival follow-up, up to data cutoff of 17 May 2008 (up to 27 months)

Outcome Measure Data Outcome Measure Data

Analysis Population Description

Analysis Population Description

FAS; only participants with EGFR IHC negative tumors were included in the analysis.

Arm/Group Title

Placebo

Erlotinib, 150 mg/Day

Arm/Group Description:

Participants completed 4 cycles (3 ...

Participants completed 4 cycles (3 ...

Arm/Group Description:

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive a placebo, PO as tablets, daily, from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive erlotinib, 150 mg/day, PO as tablets from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Overall Number of Participants Analyzed

59

62

Median (95% Confidence Interval)

Unit of Measure: months

10.2

(7.4 to 11.2)

8.6 [1]

(7.4 to NA)

[1]

The upper limit of the 95% CI could not be calculated due to the large number of censored events.

Statistical Analysis 1
Statistical Analysis 1

Statistical Analysis Overview

Comparison Group Selection

Placebo, Erlotinib, 150 mg/Day

Comments

[Not Specified]

Type of
Statistical Test

Superiority or Other

Comments

[Not Specified]

Statistical Test of Hypothesis

P-Value

0.4797

Comments

[Not Specified]

Method

Log Rank

Comments

[Not Specified]

Method of Estimation

Estimation Parameter

Hazard Ratio (HR)

Estimated Value

0.83

Confidence Interval

(2-Sided) 95%

0.49
to 1.40

Estimation Comments

[Not Specified]

18.Secondary Outcome

Title

Probable Percentage of Participants in the EGFR IHC Negative Population Remaining Alive at 1 Year (Data Cutoff 17 May 2008)

Description

OS was defined as the median time, in months, from the date of randomi...

Description

OS was defined as the median time, in months, from the date of randomization to the date of death, due to any cause. Patients who have not died at the time of the final analysis will be censored at the date the patient was last known to be alive. The 95% CI was estimated using Kaplan-Meier methodology.

Time Frame

1 year

Outcome Measure Data Outcome Measure Data

Analysis Population Description

Analysis Population Description

FAS; only participants with EGFR IHC negative tumors were included in the analysis.

Arm/Group Title

Placebo

Erlotinib, 150 mg/Day

Arm/Group Description:

Participants completed 4 cycles (3 ...

Participants completed 4 cycles (3 ...

Arm/Group Description:

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive a placebo, PO as tablets, daily, from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive erlotinib, 150 mg/day, PO as tablets from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Overall Number of Participants Analyzed

59

62

Measure Type: NumberNumber (95% Confidence Interval)

Unit of Measure: percentage of participants

20.0

(3.0 to 37.0)

42.0

(25.0 to 59.0)

19.Secondary Outcome

Title

Time to Progression (Data Cutoff 17 May 2008)

Description

The median time, in weeks, between randomization and TTP event. Partic...

Description

The median time, in weeks, between randomization and TTP event. Participants without PD were censored at the date of last tumor assessment where non-progression was documented. If a participant received a second anti-cancer therapy without prior documentation of PD, the participant was censored at the date of last tumor assessment before starting new chemotherapy.

Time Frame

Screening, BL (≤21 days after randomization), every 6 weeks thereafter until Week 48, every 12 weeks thereafter until PD, discontinuation of study treatment, or end of survival follow-up, up to data cutoff of 17 May 2008 (up to 27 months)

Outcome Measure Data Outcome Measure Data

Analysis Population Description

Analysis Population Description

FAS; participants with PD prior to randomization were excluded from analysis.

Arm/Group Title

Placebo

Erlotinib, 150 mg/Day

Arm/Group Description:

Participants completed 4 cycles (3 ...

Participants completed 4 cycles (3 ...

Arm/Group Description:

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive a placebo, PO as tablets, daily, from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive erlotinib, 150 mg/day, PO as tablets from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

TTP was defined as the time from the date of randomization to the firs...

Description

TTP was defined as the time from the date of randomization to the first date PD was recorded. For TLs, PD was defined at least a 20% increase in the SLD, taking as reference the smallest SLD recorded since treatment started or the appearance of one or more new lesions. For NTLs, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing NTLs. Participants without PD were censored at the date of last tumor assessment where non-progression was documented. If a participant received a second anti-cancer therapy without prior documentation of PD, the participant was censored at the date of last tumor assessment before starting new chemotherapy. The 95% CI was estimated using Kaplan-Meier methodology.

Time Frame

6 months

Outcome Measure Data Outcome Measure Data

Analysis Population Description

Analysis Population Description

FAS; participants with PD prior to randomization were excluded from analysis.

Arm/Group Title

Placebo

Erlotinib, 150 mg/Day

Arm/Group Description:

Participants completed 4 cycles (3 ...

Participants completed 4 cycles (3 ...

Arm/Group Description:

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive a placebo, PO as tablets, daily, from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive erlotinib, 150 mg/day, PO as tablets from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Overall Number of Participants Analyzed

447

437

Measure Type: NumberNumber (95% Confidence Interval)

Unit of Measure: percentage of participants

15.0

(11.0 to 19.0)

26.0

(21.0 to 30.0)

21.Secondary Outcome

Title

Percentage of Participants With a Best Overall Response (BOR) of Confirmed Complete Response (CR) or Partial Response (PR) According to RECIST (Data Cutoff 17 May 2008)

Description

BOR was defined as CR or PR confirmed by repeat assessments performed ...

Description

BOR was defined as CR or PR confirmed by repeat assessments performed no less than 4 weeks after the criteria for response was first met. For TLs, CR was defined as the disappearance of all TLs, and PR was defined as at least a 30% decrease in the SLD of the TLs, taking as a reference the baseline (BL) SLD. For NTLs, CR was defined as the disappearance of all NTLs and normalization of tumor marker levels. The 95% CI for one sample binomial was determined using the Pearson-Clopper method.

Time Frame

Screening, BL (≤21 days after randomization), every 6 weeks thereafter until Week 48, every 12 weeks thereafter until PD, discontinuation of study treatment, or end of survival follow-up, up to data cutoff of 17 May 2008 (up to 27 months)

Outcome Measure Data Outcome Measure Data

Analysis Population Description

Analysis Population Description

FAS; only participants with CR, PR or SD at BL as determined by the Investigator were included in the analysis.

Arm/Group Title

Placebo

Erlotinib, 150 mg/Day

Arm/Group Description:

Participants completed 4 cycles (3 ...

Participants completed 4 cycles (3 ...

Arm/Group Description:

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive a placebo, PO as tablets, daily, from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive erlotinib, 150 mg/day, PO as tablets from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Overall Number of Participants Analyzed

445

436

Measure Type: NumberNumber (95% Confidence Interval)

Unit of Measure: percentage of participants

5.4

(3.5 to 7.9)

11.9

(9.0 to 15.3)

Statistical Analysis 1
Statistical Analysis 1

Statistical Analysis Overview

Comparison Group Selection

Placebo, Erlotinib, 150 mg/Day

Comments

[Not Specified]

Type of
Statistical Test

Superiority or Other

Comments

[Not Specified]

Statistical Test of Hypothesis

P-Value

0.0006

Comments

[Not Specified]

Method

Chi-squared

Comments

[Not Specified]

Method of Estimation

Estimation Parameter

Difference in Response Rates

Estimated Value

6.53

Confidence Interval

(2-Sided) 95%

2.7
to 10.3

Estimation Comments

The approximate 95% CI for the difference of two rates was determined using the Hauck-Anderson method.

22.Secondary Outcome

Title

Percentage of Participants With a CR, PR, Stable Disease (SD), or PD According to RECIST (Data Cutoff 17 May 2008)

Description

For TLs, CR was defined as the disappearance of all TLs; PR was define...

Description

For TLs, CR was defined as the disappearance of all TLs; PR was defined as at least a 30% decrease in the SLD of the TLs, taking as a reference the BL SLD; SD was defined as neither sufficient decrease in SLD to qualify for PR nor sufficient increase in SLD to qualify for PD; and PD was defined as at least a 20% increase in the SLD of TLs, taking as reference the smallest SLD recorded since the treatment started. For NTLs, CR was defined as the disappearance of all NTLs and normalization of tumor marker levels; SD/incomplete response was defined as the persistence of 1 or more NTLs and/or maintenance of tumor marker levels above normal limits; and PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing NTLs. The 95% CI for one sample binomial was determined using the Pearson-Clopper method.

Time Frame

Screening, BL (≤21 days after randomization), every 6 weeks thereafter until Week 48, every 12 weeks thereafter until PD, discontinuation of study treatment, or end of survival follow-up, up to data cutoff of 17 May 2008 (up to 27 months)

Outcome Measure Data Outcome Measure Data

Analysis Population Description

Analysis Population Description

FAS; only participants with CR, PR or SD at BL as determined by the Investigator were included in the analysis; and 7 and 17 participants were not assessed from the Placebo and Erlotinib, 150 mg/day groups, respectively.

Arm/Group Title

Placebo

Erlotinib, 150 mg/Day

Arm/Group Description:

Participants completed 4 cycles (3 ...

Participants completed 4 cycles (3 ...

Arm/Group Description:

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive a placebo, PO as tablets, daily, from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive erlotinib, 150 mg/day, PO as tablets from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Overall Number of Participants Analyzed

445

436

Measure Type: NumberNumber (95% Confidence Interval)

Unit of Measure: percentage of participants

CR

0.7

(0.1 to 2.0)

0.9

(0.3 to 2.3)

PR

4.7

(2.9 to 7.1)

11.0

(8.2 to 14.3)

SD

45.4

(40.7 to 50.1)

48.6

(43.8 to 53.4)

PD

47.6

(42.9 to 52.4)

35.6

(31.1 to 40.2)

23.Secondary Outcome

Title

Percentage of Participants With a Response Upgrade From BL According to RECIST (Data Cutoff 17 May 2008)

Description

Response upgrade was defined by a change of PR to CR or of SD to PR or...

Description

Response upgrade was defined by a change of PR to CR or of SD to PR or CR from BL to the end of treatment. For TLs, CR was defined as the disappearance of all TLs; PR was defined as at least a 30% decrease in the SLD of the TLs, taking as a reference the BL SLD; SD was defined as neither sufficient decrease in SLD to qualify for PR nor sufficient increase in SLD to qualify for PD; and PD was defined as at least a 20% increase in the SLD of TLs, taking as reference the smallest SLD recorded since the treatment started. For NTLs, CR was defined as the disappearance of all NTLs and normalization of tumor marker levels; SD/incomplete response was defined as the persistence of 1 or more NTLs and/or maintenance of tumor marker levels above normal limits; and PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing NTLs. The 95% CI for one sample binomial was determined using the Pearson-Clopper method.

Time Frame

Screening, BL (≤21 days after randomization), every 6 weeks thereafter until Week 48, every 12 weeks thereafter until PD, discontinuation of study treatment, or end of survival follow-up, up to data cutoff of 17 May 2008 (up to 27 months)

Outcome Measure Data Outcome Measure Data

Analysis Population Description

Analysis Population Description

FAS; only participants with CR, PR or SD at BL as determined by the Investigator were included in the analysis.

Arm/Group Title

Placebo

Erlotinib, 150 mg/Day

Arm/Group Description:

Participants completed 4 cycles (3 ...

Participants completed 4 cycles (3 ...

Arm/Group Description:

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive a placebo, PO as tablets, daily, from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive erlotinib, 150 mg/day, PO as tablets from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Overall Number of Participants Analyzed

445

436

Measure Type: NumberNumber (95% Confidence Interval)

Unit of Measure: percentage of participants

1.3

(0.5 to 2.9)

5.5

(3.6 to 8.1)

Statistical Analysis 1
Statistical Analysis 1

Statistical Analysis Overview

Comparison Group Selection

Placebo, Erlotinib, 150 mg/Day

Comments

[Not Specified]

Type of
Statistical Test

Superiority or Other

Comments

[Not Specified]

Statistical Test of Hypothesis

P-Value

0.0007

Comments

[Not Specified]

Method

Chi-squared

Comments

[Not Specified]

Method of Estimation

Estimation Parameter

Difference in Response Upgrade Rates

Estimated Value

4.2

Confidence Interval

(2-Sided) 95%

1.6
to 6.7

Estimation Comments

The approximate 95% CI for the difference of two rates was determined using the Hauck-Anderson method.

24.Secondary Outcome

Title

Percentage of Participants With a Change of PR to CR or SD to PR or CR From BL to End of Treatment According to RECIST (Data Cutoff 17 May 2008)

Description

For TLs, CR was defined as the disappearance of all TLs; PR was define...

Description

For TLs, CR was defined as the disappearance of all TLs; PR was defined as at least a 30% decrease in the SLD of the TLs, taking as a reference the BL SLD; SD was defined as neither sufficient decrease in SLD to qualify for PR nor sufficient increase in SLD to qualify for PD; and PD was defined as at least a 20% increase in the SLD of TLs, taking as reference the smallest SLD recorded since the treatment started. For NTLs, CR was defined as the disappearance of all NTLs and normalization of tumor marker levels; SD/incomplete response was defined as the persistence of 1 or more NTLs and/or maintenance of tumor marker levels above normal limits; and PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing NTLs. The 95% CI for one sample binomial was determined using the Pearson-Clopper method.

Time Frame

Screening, BL (≤21 days after randomization), every 6 weeks thereafter until Week 48, every 12 weeks thereafter until PD, discontinuation of study treatment, or end of survival follow-up, up to data cutoff of 17 May 2008 (up to 27 months)

Outcome Measure Data Outcome Measure Data

Analysis Population Description

Analysis Population Description

FAS; only participants with CR, PR or SD at BL as determined by the Investigator were included in the analysis.

Arm/Group Title

Placebo

Erlotinib, 150 mg/Day

Arm/Group Description:

Participants completed 4 cycles (3 ...

Participants completed 4 cycles (3 ...

Arm/Group Description:

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive a placebo, PO as tablets, daily, from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive erlotinib, 150 mg/day, PO as tablets from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Overall Number of Participants Analyzed

445

436

Measure Type: NumberNumber (95% Confidence Interval)

Unit of Measure: percentage of participants

PR to CR

0.4

(0.1 to 1.6)

0.5

(0.1 to 1.6)

SD to PR

0.9

(0.2 to 2.3)

4.8

(3.0 to 7.3)

SD to CR

0.0

(0.0 to 0.8)

0.2

(0.0 to 1.3)

25.Secondary Outcome

Title

Percentage of Participants With CR, PR, or SD or With SD [Maintained For Greater Than (>) 12 Weeks] or CR or PR (Data Cutoff 17 May 2008)

Description

Disease control was defined as a best response of CR or PR or SD or a ...

Description

Disease control was defined as a best response of CR or PR or SD or a best response of SD for more than 12 weeks, or CR or PR. For TLs, CR was defined as the disappearance of all TLs; PR was defined as at least a 30% decrease in the SLD of the TLs, taking as a reference the BL SLD; SD was defined as neither sufficient decrease in SLD to qualify for PR nor sufficient increase in SLD to qualify for PD. For NTLs, CR was defined as the disappearance of all NTLs and normalization of tumor marker levels; SD/incomplete response was defined as the persistence of 1 or more NTLs and/or maintenance of tumor marker levels above normal limits. The 95% CI for one sample binomial was determined using the Pearson-Clopper method.

Time Frame

Screening, BL (≤21 days after randomization), every 6 weeks thereafter until Week 48, every 12 weeks thereafter until PD, discontinuation of study treatment, or end of survival follow-up, up to data cutoff of 17 May 2008 (up to 27 months)

Outcome Measure Data Outcome Measure Data

Analysis Population Description

Analysis Population Description

FAS; only participants with CR, PR or SD at BL as determined by the Investigator were included in the analysis.

Arm/Group Title

Placebo

Erlotinib, 150 mg/Day

Arm/Group Description:

Participants completed 4 cycles (3 ...

Participants completed 4 cycles (3 ...

Arm/Group Description:

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive a placebo, PO as tablets, daily, from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive erlotinib, 150 mg/day, PO as tablets from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Overall Number of Participants Analyzed

445

436

Measure Type: NumberNumber (95% Confidence Interval)

Unit of Measure: percentage of participants

CR Plus (+) PR + SD

50.8

(46.0 to 55.5)

60.6

(55.8 to 65.2)

CR + PR + SD >12 Weeks

27.4

(23.3 to 31.8)

40.8

(36.2 to 45.6)

Statistical Analysis 1
Statistical Analysis 1

Statistical Analysis Overview

Comparison Group Selection

Placebo, Erlotinib, 150 mg/Day

Comments

Analysis included CR + PR + SD rate.

Type of
Statistical Test

Superiority or Other

Comments

[Not Specified]

Statistical Test of Hypothesis

P-Value

0.0035

Comments

[Not Specified]

Method

Chi-squared

Comments

[Not Specified]

Method of Estimation

Estimation Parameter

Difference in Disease Control Rates

Estimated Value

9.8

Confidence Interval

(2-Sided) 95%

3.1
to 16.4

Estimation Comments

Approximate 95% CI for the difference of two rates was determined using the Hauck-Anderson method.

Statistical Analysis 2
Statistical Analysis 2

Statistical Analysis Overview

Comparison Group Selection

Placebo, Erlotinib, 150 mg/Day

Comments

Analysis included CR + PR + SD > 12 weeks rate.

Type of
Statistical Test

Superiority or Other

Comments

[Not Specified]

Statistical Test of Hypothesis

P-Value

<0.0001

Comments

[Not Specified]

Method

Chi-squared

Comments

[Not Specified]

Method of Estimation

Estimation Parameter

Difference in Disease Control Rates

Estimated Value

13.4

Confidence Interval

(2-Sided) 95%

7.1
to 19.7

Estimation Comments

Approximate 95% CI for the difference of two rates was determined using the Hauck-Anderson method.

LCS scores were obtained from a 7-item questionnaire from the Function...

Description

LCS scores were obtained from a 7-item questionnaire from the Functional Assessment of Cancer Therapy - Lung (FACT-L) version (V) 4. Participants responded to questions assessing symptoms commonly reported by lung cancer patients; such as shortness of breath, loss of weight, and tightness in chest; on a scale from 0-4, where 0 equaled (=) "not at all" and 4 = "very much." The participants' responses were summed to result in an overall score, where a higher score indicated more severe symptoms. A change of 2 to 3 points in score was determined to be a clinically meaningful decline.

Time Frame

Screening, BL (≤21 days after randomization), every 6 weeks thereafter until Week 48, every 12 weeks thereafter until PD, discontinuation of study treatment, or end of survival follow-up, up to data cutoff of 17 May 2008 (up to 27 months)

Outcome Measure Data Outcome Measure Data

Analysis Population Description

Analysis Population Description

FAS; 56 and 48 participants were not evaluated for this outcome measure from the Placebo and Erlotinib groups, respectively.

Arm/Group Title

Placebo

Erlotinib, 150 mg/Day

Arm/Group Description:

Participants completed 4 cycles (3 ...

Participants completed 4 cycles (3 ...

Arm/Group Description:

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive a placebo, PO as tablets, daily, from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive erlotinib, 150 mg/day, PO as tablets from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Overall Number of Participants Analyzed

395

390

Measure Type: Number

Unit of Measure: percentage of participants

44.1

47.7

27.Secondary Outcome

Title

Time to Symptom Progression (Data Cutoff 17 May 2008)

Description

The median time, in weeks, from the date of randomization to the date ...

Description

The median time, in weeks, from the date of randomization to the date of documented clinically meaningful decline in LCS from BL or death, whichever occurred first. LCS scores were obtained from a 7-item questionnaire from the FACT-L V 4. Participants responded to questions assessing symptoms commonly reported by lung cancer patients; such as shortness of breath, loss of weight, and tightness in chest; on a scale from 0-4, where 0 = "not at all" and 4 = "very much." The participants' responses were summed to result in an overall score, where a higher score indicated more severe symptoms. A change of 2 to 3 points in score was determined to be a clinically meaningful decline. The 95% CI was determined using Kaplan-Meier methodology.

Time Frame

Screening, BL (≤21 days after randomization), every 6 weeks thereafter until Week 48, every 12 weeks thereafter until PD, discontinuation of study treatment, or end of survival follow-up, up to data cutoff of 17 May 2008 (up to 27 months)

Outcome Measure Data Outcome Measure Data

Analysis Population Description

Analysis Population Description

FAS

Arm/Group Title

Placebo

Erlotinib, 150 mg/Day

Arm/Group Description:

Participants completed 4 cycles (3 ...

Participants completed 4 cycles (3 ...

Arm/Group Description:

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive a placebo, PO as tablets, daily, from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive erlotinib, 150 mg/day, PO as tablets from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

LCS scores were obtained from a 7-item questionnaire from the FACT-L V...

Description

LCS scores were obtained from a 7-item questionnaire from the FACT-L V 4. Participants responded to questions assessing symptoms commonly reported by lung cancer patients; such as shortness of breath, loss of weight, and tightness in chest; on a scale from 0-4, where 0 = "not at all" and 4 = "very much." The participants' responses were summed to result in an overall score, where a higher score indicated more severe symptoms. A change of 2 to 3 points in score was determined to be a clinically meaningful decline. The 95% CI was estimated using Kaplan-Meier methodology.

Time Frame

6 months

Outcome Measure Data Outcome Measure Data

Analysis Population Description

Analysis Population Description

FAS

Arm/Group Title

Placebo

Erlotinib, 150 mg/Day

Arm/Group Description:

Participants completed 4 cycles (3 ...

Participants completed 4 cycles (3 ...

Arm/Group Description:

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive a placebo, PO as tablets, daily, from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive erlotinib, 150 mg/day, PO as tablets from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Overall Number of Participants Analyzed

395

390

Measure Type: NumberNumber (95% Confidence Interval)

Unit of Measure: percentage of participants

35.0

(27.0 to 42.0)

41.0

(34.0 to 47.0)

29.Secondary Outcome

Title

Percentage of Participants With Deterioration Assessed Using the Trial Outcome Index (Data Cutoff 17 May 2008)

Description

The Trial Outcome Index (TOI) was defined as the sum of the scores of ...

Description

The Trial Outcome Index (TOI) was defined as the sum of the scores of the Physical Well-Being (PWB), Functional Well-Being (FWB), and LCS. PWB, FWB, and LCS scores were obtained from 7-item questionnaires from the FACT-L V 4. Participants responded to questions assessing symptoms on a scale from 0-4, where 0 = "not at all" and 4 = "very much." Higher score indicated more severe symptoms. A clinically meaningful decline in TOI score was defined as at least a 6 point decline from BL. Participants without a clinically meaningful decline in TOI at the time of analysis were censored at the time of the last FACT-L assessment.

Time Frame

Screening, BL (≤21 days after randomization), every 6 weeks thereafter until Week 48, every 12 weeks thereafter until PD, discontinuation of study treatment, or end of survival follow-up, up to data cutoff of 17 May 2008 (up to 27 months)

Outcome Measure Data Outcome Measure Data

Analysis Population Description

Analysis Population Description

FAS; 59 and 49 participants were not evaluated for this outcome measure from the Placebo and Erlotinib groups, respectively.

Arm/Group Title

Placebo

Erlotinib, 150 mg/Day

Arm/Group Description:

Participants completed 4 cycles (3 ...

Participants completed 4 cycles (3 ...

Arm/Group Description:

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive a placebo, PO as tablets, daily, from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive erlotinib, 150 mg/day, PO as tablets from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Overall Number of Participants Analyzed

392

389

Measure Type: Number

Unit of Measure: percentage of participants

43.1

50.9

30.Secondary Outcome

Title

Time to Deterioration in TOI (Data Cutoff 17 May 2008)

Description

The median time, in weeks, from the date of randomization until a clin...

Description

The median time, in weeks, from the date of randomization until a clinically meaningful decline from BL in TOI or death, whichever occurred first. TOI was defined as the sum of PWB, FWB, and LCS scores, which were obtained from 7-item questionnaires from the FACT-L V 4. Participants responded to questions assessing symptoms on a scale from 0-4, where 0 = "not at all" and 4 = "very much." Higher score indicated more severe symptoms. A clinically meaningful decline in TOI score was defined as at least a 6 point decline from BL Participants without a clinically meaningful decline in TOI at the time of analysis were censored at the time of the last FACT-L assessment. The 95% CI was determined using Kaplan-Meier methodology.

Time Frame

Screening, BL (≤21 days after randomization), every 6 weeks thereafter until Week 48, every 12 weeks thereafter until PD, discontinuation of study treatment, or end of survival follow-up, up to data cutoff of 17 May 2008 (up to 27 months)

Outcome Measure Data Outcome Measure Data

Analysis Population Description

Analysis Population Description

FAS

Arm/Group Title

Placebo

Erlotinib, 150 mg/Day

Arm/Group Description:

Participants completed 4 cycles (3 ...

Participants completed 4 cycles (3 ...

Arm/Group Description:

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive a placebo, PO as tablets, daily, from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive erlotinib, 150 mg/day, PO as tablets from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

TOI was defined as the sum of the scores of the PWB, FWB, and LCS. PWB...

Description

TOI was defined as the sum of the scores of the PWB, FWB, and LCS. PWB, FWB, and LCS scores were obtained from 7-item questionnaires from the FACT-L V 4. Participants responded to questions assessing symptoms on a scale from 0-4, where 0 = "not at all" and 4 = "very much." Higher score indicated more severe symptoms. A clinically meaningful decline in TOI score was defined as at least a 6 point decline from BL. Participants without a clinically meaningful decline in TOI at the time of analysis were censored at the time of the last FACT-L assessment. The 95% CI was estimated using Kaplan-Meier methodology.

Time Frame

6 months

Outcome Measure Data Outcome Measure Data

Analysis Population Description

Analysis Population Description

FAS

Arm/Group Title

Placebo

Erlotinib, 150 mg/Day

Arm/Group Description:

Participants completed 4 cycles (3 ...

Participants completed 4 cycles (3 ...

Arm/Group Description:

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive a placebo, PO as tablets, daily, from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive erlotinib, 150 mg/day, PO as tablets from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Overall Number of Participants Analyzed

392

389

Measure Type: NumberNumber (95% Confidence Interval)

Unit of Measure: percentage of participants

41.0

(34.0 to 48.0)

39.0

(33.0 to 45.0)

32.Secondary Outcome

Title

Percentage of Participants With Deterioration in Quality of Life Assessed Using TOI, SWB, and EWB (Data Cutoff 17 May 2008)

Description

Deterioration in quality of life (QoL) was defined as a clinically mea...

Description

Deterioration in quality of life (QoL) was defined as a clinically meaningful decline in the total FACT-L score, the sum of the TOI, Social/Family Well-Being (SWB) and Emotional Well-Being (EWB) of the FACT-L questionnaires. TOI (PWB + FWB + LCS), SWB and EWB scores were obtained from 7-item (6-item in the case of EWB) questionnaires from the FACT-L V 4. Participants responded to questions assessing symptoms on a scale from 0-4, where 0 = "not at all" and 4 = "very much." Higher score indicated more severe symptoms. A clinically meaningful decline in FACT-L score was defined as at least a 6 point decline from BL. Participants without a clinically meaningful decline in TOI at the time of analysis were censored at the time of the last FACT-L.

Time Frame

Screening, BL (≤21 days after randomization), every 6 weeks thereafter until Week 48, every 12 weeks thereafter until PD, discontinuation of study treatment, or end of survival follow-up, up to data cutoff of 17 May 2008 (up to 27 months)

Outcome Measure Data Outcome Measure Data

Analysis Population Description

Analysis Population Description

FAS; 62 and 51 participants were not evaluated for this outcome measure from the Placebo and Erlotinib groups, respectively,

Arm/Group Title

Placebo

Erlotinib, 150 mg/Day

Arm/Group Description:

Participants completed 4 cycles (3 ...

Participants completed 4 cycles (3 ...

Arm/Group Description:

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive a placebo, PO as tablets, daily, from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive erlotinib, 150 mg/day, PO as tablets from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Overall Number of Participants Analyzed

389

387

Measure Type: Number

Unit of Measure: percentage of participants

51.7

55.3

33.Secondary Outcome

Title

Time to Deterioration in QoL (Data Cutoff 17 May 2008)

Description

The median time, in weeks, from the date of randomization until a clin...

Description

The median time, in weeks, from the date of randomization until a clinically meaningful decline from BL in total FACT-L or death, whichever occurred first. Total FACT-L score was defined as the sum of the TOI, SWB and EWB of the FACT-L questionnaires. TOI (PWB + FWB + LCS), SWB and EWB scores were obtained from 7-item (6-item in the case of EWB) questionnaires from the FACT-L V 4. Participants responded to questions assessing symptoms on a scale from 0-4, where 0 = "not at all" and 4 = "very much." Higher score indicated more severe symptoms. A clinically meaningful decline in FACT-L score was defined as at least a 6 point decline from BL. Participants without a clinically meaningful decline in TOI at the time of analysis were censored at the time of the last FACT-L assessment. The 95% CI was determined using Kaplan-Meier methodology.

Time Frame

Screening, BL (≤21 days after randomization), every 6 weeks thereafter until Week 48, every 12 weeks thereafter until PD, discontinuation of study treatment, or end of survival follow-up, up to data cutoff of 17 May 2008 (up to 27 months)

Outcome Measure Data Outcome Measure Data

Analysis Population Description

Analysis Population Description

FAS

Arm/Group Title

Placebo

Erlotinib, 150 mg/Day

Arm/Group Description:

Participants completed 4 cycles (3 ...

Participants completed 4 cycles (3 ...

Arm/Group Description:

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive a placebo, PO as tablets, daily, from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive erlotinib, 150 mg/day, PO as tablets from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Deterioration in QoL was defined as a clinically meaningful decline in...

Description

Deterioration in QoL was defined as a clinically meaningful decline in the total FACT-L score, the sum of the TOI, SWB and EWB of the FACT-L questionnaires. TOI (PWB + FWB + LCS), SWB and EWB scores were obtained from 7-item (6-item in the case of EWB) questionnaires from the FACT-L V 4. Participants responded to questions assessing symptoms on a scale from 0-4, where 0 = "not at all" and 4 = "very much." Higher score indicated more severe symptoms. A clinically meaningful decline in FACT-L score was defined as at least a 6 point decline from BL. Participants without a clinically meaningful decline in TOI at the time of analysis were censored at the time of the last FACT-L. The 95% CI was estimated using Kaplan-Meier methodology.

Time Frame

6 months

Outcome Measure Data Outcome Measure Data

Analysis Population Description

Analysis Population Description

FAS

Arm/Group Title

Placebo

Erlotinib, 150 mg/Day

Arm/Group Description:

Participants completed 4 cycles (3 ...

Participants completed 4 cycles (3 ...

Arm/Group Description:

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive a placebo, PO as tablets, daily, from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive erlotinib, 150 mg/day, PO as tablets from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Screening, BL (≤21 days after randomization), every 6 weeks thereafter until Week 48, every 12 weeks thereafter until PD, discontinuation of study treatment, or end of survival follow-up, up to data cutoff of 17 May 2008 (up to 27 months)

Outcome Measure Data Outcome Measure Data

Analysis Population Description

Analysis Population Description

FAS; n=number of participants assessed for the given parameter at the specified timepoint.

Arm/Group Title

Placebo

Erlotinib, 150 mg/Day

Arm/Group Description:

Participants completed 4 cycles (3 ...

Participants completed 4 cycles (3 ...

Arm/Group Description:

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive a placebo, PO as tablets, daily, from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive erlotinib, 150 mg/day, PO as tablets from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Overall Number of Participants Analyzed

397

392

Mean (Standard Deviation)

Unit of Measure: score on a scale

BL: Physical Well-Being (n=397,392)

20.85
(4.817)

20.96
(4.781)

BL: Social Well-Being (n=397,392)

20.84
(5.496)

20.98
(5.285)

BL: Emotional Well-Being (n=397,393)

16.92
(4.534)

16.77
(4.862)

BL: Functional Well-Being (n=397,393)

16.15
(5.488)

16.84
(5.514)

BL: FACT-L Subscale Score (n=397,391)

24.17
(4.892)

24.46
(4.697)

BL: Lung Cancer Subscale Score (n=397,391)

19.82
(4.188)

20.07
(4.240)

BL: Total FACT-General (FACT-G) Score (n=396,391)

74.68
(14.787)

75.52
(14.612)

BL: Trial Outcome Index (n=396,390)

56.83
(11.830)

57.90
(11.682)

BL: Total FACT-L Score (n=395,389)

98.85
(18.007)

100.02
(17.751)

Week 6: Physical Well-Being (n=274,304)

21.44
(5.117)

20.69
(5.180)

Week 6: Social Well-Being (n=274,303

20.62
(5.437)

21.43
(5.178)

Week 6: Emotional Well-Being (n=275,302)

16.53
(4.587)

17.17
(4.748)

Week 6: Functional Well-Being (n=275,302)

16.41
(5.234)

16.87
(5.614)

Week 6: FACT-L Subscale Score (n=275,300)

24.45
(5.231)

24.80
(5.000)

Week 6: Lung Cancer Subscale Score (n=275,300)

19.78
(4.463)

20.13
(4.336)

Week 6: Total FACT-G Score (n=274,300)

74.82
(14.380)

76.14
(15.132)

Week 6: Trial Outcome Index (n=274,299)

57.59
(12.292)

57.64
(12.482)

Week 6: Total FACT-L Score (n=274,297)

99.27
(17.857)

100.95
(18.360)

Week 12: Physical Well-Being (n=144,194)

21.93
(4.734)

20.78
(5.368)

Week 12: Social Well-Being (n=143,194)

20.38
(5.637)

20.04
(5.691)

Week 12: Emotional Well-Being (n=144,194)

17.21
(4.376)

16.85
(4.521)

Week 12: Functional Well-Being (n=144,196)

17.04
(5.770)

16.35
(5.745)

Week 12: FACT-L Subscale Score (n=144,196)

25.15
(4.735)

24.19
(5.323)

Week 12: Lung Cancer Subscale Score (n=144,196)

20.22
(4.015)

19.50
(4.600)

Week 12: Total FACT-G Score (n=144,192)

76.42
(14.889)

74.06
(15.754)

Week 12: Trial Outcome Index (n=144,194)

59.19
(12.129)

56.57
(13.276)

Week 12: Total FACT-L Score (n=144,192)

101.56
(17.824)

98.30
(19.337)

Week 18: Physical Well-Being (n=86,143)

21.60
(4.883)

21.40
(4.945)

Week 18: Social Well-Being (n=86,143)

21.08
(5.328)

19.94
(6.130)

Week 18: Emotional Well-Being (n=86,143)

17.33
(4.717)

17.14
(4.356)

Week 18: Functional Well-Being (n=86,143)

16.89
(5.289)

16.83
(5.553)

Week 18: FACT-L Subscale Score (n=86,143)

25.44
(4.645)

24.52
(5.344)

Week 18: Lung Cancer Subscale Score (n=86,143)

20.28
(4.003)

19.64
(4.635)

Week 18: Total FACT-G Score (n=86,143)

76.89
(14.385)

75.31
(16.648)

Week 18: Trial Outcome Index (n=86,143)

58.76
(11.492)

57.87
(12.803)

Week 18: Total FACT-L Score (n=86,143)

102.33
(17.502)

99.83
(20.558)

Week 24: Physical Well-Being (n=59,101)

21.78
(4.665)

21.21
(4.898)

Week 24: Social Well-Being (n=59,101)

20.79
(5.641)

20.49
(5.251)

Week 24: Emotional Well-Being (n=59,100)

16.86
(4.880)

16.54
(4.615)

Week 24: Functional Well-Being (n=59,100)

17.14
(6.062)

17.23
(5.300)

Week 24: FACT-L Subscale Score (n=59,101)

25.18
(5.126)

25.13
(5.245)

Week 24: Lung Cancer Subscale Score (n=59,101)

20.07
(4.246)

19.94
(4.487)

Week 24: Total FACT-G Score (n=59,99)

76.58
(16.091)

75.50
(15.754)

Week 24: Trial Outcome Index (n=59,100)

58.99
(11.837)

58.37
(12.686)

Week 24: Total FACT-L Score (n=59,99)

101.75
(19.347)

100.69
(19.831)

Week 30: Physical Well-Being (n=37,66)

21.74
(4.153)

21.77
(4.576)

Week 30: Social Well-Being (n=37,66)

20.50
(5.180)

20.74
(5.491)

Week 30: Emotional Well-Being (n=37,66)

16.37
(4.164)

17.23
(4.675)

Week 30: Functional Well-Being (n=37,66)

17.92
(5.082)

17.93
(5.510)

Week 30: FACT-L Subscale Score (n=37,66)

25.90
(3.484)

25.86
(4.817)

Week 30: Lung Cancer Subscale Score (n=37,66)

20.66
(3.073)

20.61
(4.393)

Week 30: Total FACT-G Score (n=37,66)

76.54
(11.915)

77.66
(15.078)

Week 30: Trial Outcome Index (n=37,66)

60.32
(9.753)

60.30
(11.876)

Week 30: Total FACT-L Score (n=37,66)

102.44
(14.063)

103.52
(18.367)

Week 36: Physical Well-Being (n=25,47)

21.60
(3.317)

22.26
(4.480)

Week 36: Social Well-Being (n=25,47)

20.02
(5.769)

20.15
(4.988)

Week 36: Emotional Well-Being (n=25,47)

17.31
(3.736)

17.54
(4.540)

Week 36: Fuctional Well-Being (n=25,47)

16.06
(4.287)

18.06
(5.720)

Week 36: FACT-L Subscale Score (n=25,47)

24.48
(4.089)

25.83
(5.305)

Week 36: Lung Cancer Subscale Score (n=25,47)

19.36
(3.893)

20.55
(4.463)

Week 36: Total FACT-G Score (n=25,47)

74.99
(11.066)

78.02
(15.688)

Week 36: Trial Outcome Index (n=25,47)

57.02
(9.426)

60.87
(11.963)

Week 36: Total FACT-L Score (n=25,47)

99.27
(13.672)

103.86
(19.244)

Week 42: Physical Well-Being (n=19,35)

21.76
(3.592)

22.19
(5.035)

Week 42: Social Well-Being (n=19,35)

18.45
(6.262)

20.40
(5.234)

Week 42: Emotional Well-Being (n=19,35)

16.95
(4.089)

17.43
(4.984)

Week 42: Functional Well-Being (n=19,35)

15.32
(3.902)

18.57
(5.500)

Week 42: FACT-L Subscale Score (n=19,35)

24.63
(4.448)

26.67
(5.357)

Week 42: Lung Cancer Subscale Score (n=19,35)

19.50
(4.092)

21.21
(4.607)

Week 42: FACT-G Score (n=19,35)

72.74
(12.406)

78.59
(16.316)

Week 42: Trial Outcome Index (n=19,35)

56.58
(9.562)

61.97
(12.622)

Week 42: FACT-L Score (n=19,35)

97.11
(14.951)

105.25
(20.385)

Week 48: Physical Well-Being (n=13,29)

21.38
(4.154)

23.23
(4.016)

Week 48: Social Well-Being (n=13,29)

17.23
(7.567)

20.24
(5.569)

Week 48: Emotional Well-Being (n=13,29)

18.69
(3.011)

17.59
(4.903)

Week 48: Functional Well-Being (n=13,29)

14.15
(2.672)

18.48
(4.501)

Week 48: FACT-L Subscale Score (n=12,29)

23.35
(3.647)

26.80
(5.591)

Week 48: Lung Cancer Subscale Score (n=12,29)

18.75
(3.646)

21.21
(4.967)

Week 48: FACT-G Score (n=12,29)

71.46
(12.069)

79.53
(14.672)

Week 48: Trial Outcome Index (n=12,29)

54.58
(9.140)

62.92
(11.105)

Week 48: FACT-L Score (n=12,29)

96.19
(14.394)

106.33
(18.701)

Week 60: Physical Well-Being (n=9,17)

22.67
(4.664)

23.65
(4.212)

Week 60: Social Well-Being (n=9,17)

17.78
(6.405)

21.31
(6.530)

Week 60: Emotional Well-Being (n=9,17)

16.78
(3.232)

19.12
(3.638)

Week 60: Functional Well-Being (n=9,17)

15.11
(3.408)

18.65
(6.828)

Week 60: FACT-L Subscale Score (n=9,17)

23.43
(5.010)

25.99
(6.844)

Week 60: Lung Cancer Subscale Score (n=9,17)

17.89
(3.919)

20.47
(5.959)

Week 60: Total FACT-G Score (n=9,17)

72.34
(11.607)

82.73
(17.803)

Week 60: Trial Outcome Index (n=9,17)

55.67
(9.695)

62.76
(14.316)

Week 60: Total FACT-L Score (n=9,17)

95.77
(15.703)

108.71
(23.069)

Week 72: Physical Well-Being (n=6,8)

22.17
(4.997)

23.25
(4.097)

Week 72: Social Well-Being (n=6,8)

19.00
(7.251)

21.44
(5.852)

Week 72: Emotional Well-Being (n=6,8)

17.17
(2.401)

18.25
(5.007)

Week 72: Functional Well-Being (n=6,8)

15.22
(4.457)

16.50
(5.855)

Week 72: FACT-L Subscale Score (n=6,8)

21.23
(5.154)

26.48
(6.185)

Week 72: Lung Cancer Subscale Score (n=6,8)

17.17
(4.021)

21.40
(5.724)

Week 72: Total FACT-G Score (n=6,8)

73.67
(14.820)

79.44
(16.176)

Week 72: Trial Outcome Index (n=6,8)

54.67
(11.911)

61.15
(14.343)

Week 72: Total FACT-L Score (n=6,8)

94.90
(18.833)

105.92
(21.282)

Week 84: Physical Well-Being (n=1,0)

20.00 [1]
(NA)

NA [2]
(NA)

Week 84: Social Well-Being (n=1,0)

14.00 [3]
(NA)

NA [2]
(NA)

Week 84: Emotional Well-Being (n=1,0)

13.00 [3]
(NA)

NA [2]
(NA)

Week 84: Functional Well-Being (n=1,0)

18.00 [3]
(NA)

NA [2]
(NA)

Week 84: FACT-L Subscale Score (n=1,0)

17.00 [3]
(NA)

NA [2]
(NA)

Week 84: Lung Cancer Subscale Score (n=1,0)

13.00 [3]
(NA)

NA [2]
(NA)

Week 84: Total FACT-G Score (n=1,0)

65.00 [3]
(NA)

NA [2]
(NA)

Week 84: Trial Outcome Index (n=1,0)

51.00 [3]
(NA)

NA [2]
(NA)

Week 84: Total FACT-L Score (n=1,0)

82.00 [3]
(NA)

NA [2]
(NA)

Off Trtmt: Physical Well-Being (n=265,215)

19.57
(5.668)

18.50
(5.534)

Off Trtmt: Social Well-Being (n=263,216)

20.01
(5.380)

20.68
(5.265)

Off Trtmt: Emotional Well-Being (n=265,216)

14.76
(5.157)

15.11
(5.183)

Off Trtmt: Functional Well-Being (n=265,216)

14.90
(5.893)

14.58
(5.934)

Off Trtmt: FACT-L Subscale Score (n=264,214)

22.80
(5.268)

22.88
(4.911)

Off Trtmt: Lung Cancer Subscale Score (n=264,214)

18.06
(4.629)

18.16
(4.383)

Off Trtmt:Total FACT-G Score (n=261,214)

69.29
(15.730)

68.94
(15.669)

Off Trtmt:Trial Outcome Index (n=263,213)

52.61
(13.475)

51.34
(12.974)

Off Trtmt:Total FACT-L Score (n=260,212)

92.14
(19.324)

91.89
(18.738)

[1]

Standard deviation (SD) not calculated as only 1 participant was analyzed.

[2]

Zero participants analyzed

[3]

SD not calculated as only 1 participant was analyzed.

36.Secondary Outcome

Title

Change From BL in FACT-L Scores (Data Cutoff 17 May 2008)

Description

Total FACT-L score=sum of TOI, SWB, and EWB of FACT-L questionnaires. ...

Screening, BL (≤21 days after randomization), every 6 weeks thereafter until Week 48, every 12 weeks thereafter until PD, discontinuation of study treatment, or end of survival follow-up, up to data cutoff of 17 May 2008 (up to 27 months)

Outcome Measure Data Outcome Measure Data

Analysis Population Description

Analysis Population Description

FAS; n=number of participants assessed for the given parameter at the specified timepoint.

Arm/Group Title

Placebo

Erlotinib, 150 mg/Day

Arm/Group Description:

Participants completed 4 cycles (3 ...

Participants completed 4 cycles (3 ...

Arm/Group Description:

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive a placebo, PO as tablets, daily, from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive erlotinib, 150 mg/day, PO as tablets from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Adverse events (AEs) were recorded from Day 1 (after randomization) through the end of study, up to 27 months. Serious adverse events (SAEs) were recorded from Day 1 (after randomization) through the second data cut-off, up to 71 months.

Adverse Event Reporting Description

All participants who received at least 1 dose of investigational treatment and had at least 1 safety follow-up, whether prematurely withdrawn or not, were included in the safety analysis.

Arm/Group Title

Placebo

Erlotinib, 150 mg/Day

Arm/Group Description

Participants completed 4 cycles (3 ...

Participants completed 4 cycles (3 ...

Arm/Group Description

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive a placebo, PO as tablets, daily, from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

Participants completed 4 cycles (3 or 4 week cycles) of a standard platinum based non-investigational chemotherapy according to local practice and in concordance with the local labeling instructions (chemotherapy run-in period). Participants who completed all 4 cycles of chemotherapy run-in without PD according to RECIST were randomized to receive erlotinib, 150 mg/day, PO as tablets from randomization until PD, death, unacceptable toxicity, or end of study, up to 27 months.

All-Cause Mortality

Placebo

Erlotinib, 150 mg/Day

Affected / at Risk (%)

Affected / at Risk (%)

Total

--/--

--/--

Serious Adverse Events Serious Adverse Events

Placebo

Erlotinib, 150 mg/Day

Affected / at Risk (%)

Affected / at Risk (%)

Total

34/445 (7.64%)

49/433 (11.32%)

Blood and lymphatic system disorders

Anaemia * 1

0/445 (0.00%)

1/433 (0.23%)

Cardiac disorders

Cardio-respiratory arrest * 1

0/445 (0.00%)

2/433 (0.46%)

Cardiac failure * 1

0/445 (0.00%)

1/433 (0.23%)

Cardiac tamponade * 1

1/445 (0.22%)

0/433 (0.00%)

Left ventricular dysfunction * 1

0/445 (0.00%)

1/433 (0.23%)

Myocardial infarction * 1

1/445 (0.22%)

0/433 (0.00%)

Aortic aneurysm * 1

0/445 (0.00%)

1/433 (0.23%)

Eye disorders

Diplopia * 1

1/445 (0.22%)

0/433 (0.00%)

Gastrointestinal disorders

Diarrhoea * 1

0/445 (0.00%)

4/433 (0.92%)

Vomiting * 1

2/445 (0.45%)

0/433 (0.00%)

Dysphagia * 1

1/445 (0.22%)

0/433 (0.00%)

Gastric perforation * 1

0/445 (0.00%)

1/433 (0.23%)

Gastric ulcer perforation * 1

0/445 (0.00%)

1/433 (0.23%)

Haematemesis * 1

0/445 (0.00%)

1/433 (0.23%)

General disorders

Asthenia * 1

1/445 (0.22%)

0/433 (0.00%)

Chest pain * 1

0/445 (0.00%)

1/433 (0.23%)

Drowning * 1

0/445 (0.00%)

1/433 (0.23%)

Pyrexia * 1

0/445 (0.00%)

1/433 (0.23%)

Sudden death * 1

0/445 (0.00%)

1/433 (0.23%)

Hepatobiliary disorders

Cholelithiasis * 1

0/445 (0.00%)

1/433 (0.23%)

Infections and infestations

Pneumonia * 1

4/445 (0.90%)

7/433 (1.62%)

Bronchitis * 1

2/445 (0.45%)

0/433 (0.00%)

Lower respiratory tract infection * 1

1/445 (0.22%)

1/433 (0.23%)

Respiratory tract infection * 1

1/445 (0.22%)

1/433 (0.23%)

Catheter sepsis * 1

1/445 (0.22%)

0/433 (0.00%)

Cellulitis * 1

0/445 (0.00%)

2/433 (0.46%)

Empyema * 1

1/445 (0.22%)

0/433 (0.00%)

Lung abscess * 1

0/445 (0.00%)

1/433 (0.23%)

Nocardiosis * 1

1/445 (0.22%)

0/433 (0.00%)

Pyelonephritis acute * 1

0/445 (0.00%)

1/433 (0.23%)

Sepsis * 1

0/445 (0.00%)

1/433 (0.23%)

Staphylococcal abscess * 1

0/445 (0.00%)

1/433 (0.23%)

Upper respiratory tract infection * 1

0/445 (0.00%)

1/433 (0.23%)

Colitis * 1

0/445 (0.00%)

1/433 (0.23%)

Injury, poisoning and procedural complications

Femur fracture * 1

2/445 (0.45%)

0/433 (0.00%)

Spinal compression fracture * 1

0/445 (0.00%)

1/433 (0.23%)

Investigations

Alanine aminotransferase increased * 1

0/445 (0.00%)

1/433 (0.23%)

Aspartate aminotransferase increased * 1

0/445 (0.00%)

1/433 (0.23%)

Metabolism and nutrition disorders

Anorexia * 1

0/445 (0.00%)

1/433 (0.23%)

Dehydration * 1

0/445 (0.00%)

1/433 (0.23%)

Musculoskeletal and connective tissue disorders

Muscular weakness * 1

1/445 (0.22%)

0/433 (0.00%)

Pain in extremity * 1

1/445 (0.22%)

0/433 (0.00%)

Nervous system disorders

Cerebrovascular accident * 1

1/445 (0.22%)

1/433 (0.23%)

Dizziness * 1

0/445 (0.00%)

1/433 (0.23%)

Intracranial pressure increased * 1

0/445 (0.00%)

1/433 (0.23%)

Neuralgia * 1

0/445 (0.00%)

1/433 (0.23%)

Neuropathy peripheral * 1

0/445 (0.00%)

1/433 (0.23%)

Peripheral motor neuropathy * 1

0/445 (0.00%)

1/433 (0.23%)

Sciatica * 1

1/445 (0.22%)

0/433 (0.00%)

Syncope * 1

0/445 (0.00%)

1/433 (0.23%)

Psychiatric disorders

Depression * 1

0/445 (0.00%)

1/433 (0.23%)

Panic attack * 1

0/445 (0.00%)

1/433 (0.23%)

Renal and urinary disorders

Renal failure acute * 1

0/445 (0.00%)

1/433 (0.23%)

Urogenital haemorrhage * 1

0/445 (0.00%)

1/433 (0.23%)

Respiratory, thoracic and mediastinal disorders

Dyspnoea * 1

2/445 (0.45%)

2/433 (0.46%)

Haemoptysis * 1

2/445 (0.45%)

1/433 (0.23%)

Interstitial lung disease * 1

0/445 (0.00%)

2/433 (0.46%)

Pleural effusion * 1

1/445 (0.22%)

1/433 (0.23%)

Pulmonary embolism * 1

2/445 (0.45%)

0/433 (0.00%)

Bronchospasm * 1

1/445 (0.22%)

0/433 (0.00%)

Chronic obstructive pulmonary disease * 1

1/445 (0.22%)

0/433 (0.00%)

Epistaxis * 1

1/445 (0.22%)

0/433 (0.00%)

Pleural fistula * 1

0/445 (0.00%)

1/433 (0.23%)

Pneumonia aspiration * 1

1/445 (0.22%)

0/433 (0.00%)

Pulmonary fibrosis * 1

0/445 (0.00%)

1/433 (0.23%)

Respiratory failure * 1

0/445 (0.00%)

1/433 (0.23%)

Skin and subcutaneous tissue disorders

Rash * 1

0/445 (0.00%)

2/433 (0.46%)

Vascular disorders

Peripheral ischaemia * 1

1/445 (0.22%)

1/433 (0.23%)

Arterial thrombosis * 1

1/445 (0.22%)

0/433 (0.00%)

Arteritis * 1

1/445 (0.22%)

0/433 (0.00%)

Deep vein thrombosis * 1

1/445 (0.22%)

0/433 (0.00%)

Iliac artery thrombosis * 1

0/445 (0.00%)

1/433 (0.23%)

*

Indicates events were collected by non-systematic assessment

1

Term from vocabulary, MedDRA (11.0)

Other (Not Including Serious) Adverse Events Other (Not Including Serious) Adverse Events

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts
the PI's rights to discuss or publish trial results after the trial is completed.

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.